Stage-Specific Survival From Esophageal Cancer in China and Implications for Control Strategies: A Systematic Review and Meta-Analyses

Abstract

Background and aims: Esophageal cancer claims more than 500,000 deaths worldwide, with half occurring in China. We aimed to synthesize existing evidence on stage-specific survival from this cancer in China to inform cancer control strategies.

Methods: English and Chinese literature databases were systematically searched to identify original research published up to May 31, 2019 that reported stage-specific survival from esophageal cancer in China. Two meta-analyses were performed using random-effects models to summarize stage-specific survival differences on relative and absolute scales. The number of esophageal cancer deaths that might have been prevented by early detection in China, in 2018, was estimated assuming 2 different downstaging scenarios.

Results: One hundred fifty eligible studies were identified, 97 had non-overlapping study populations (83,063 participants), 47 were included in the meta-analysis of hazard ratios, and 26 in the meta-analysis of survival probabilities. Late-stage (III-IV) was associated with 92% higher hazard of death compared with early-stage (0-II) (95% confidence interval 1.62-2.28), corresponding to an absolute 5-year survival difference of 31.2% (29.9%-32.4%). In all, 5.2% esophageal cancer deaths could have been prevented in China, in 2018, if the observed stage distribution at diagnosis (∼50% early-stage) was shifted to the real-life conditions of a population-based endoscopic screening program (∼60% early-stage) and 26.9% if shifted to that observed in the controlled setting of a randomized trial (∼90% early-stage).

Conclusion: Shifting downwards the stage distribution of esophageal cancer through screening would bring moderate reductions in mortality from the disease. Treatment improvements for early-stage patients are needed to reduce further mortality from this cancer.

Keywords: Avoidable deaths; Esophageal cancer; Meta-analysis; Stage-specific survival; Systematic review.

Figure 1

PRISMA flowchart of retrieved, excluded, and included studies in the systematic review and in the meta-analyses of relative and absolute stage-specific differences in survival from esophageal cancer in China (numbers in italics within square brackets refer to the number of non-overlapping studies—see Methods section). ∗No eligible records were identified by the search of annual reports of the National Central Cancer Registry (2010–2018) and Taiwan (2003–2017), Hong Kong (2009–2017), and Macao (2003–2016) cancer registries. †One study retrieved from the English databases contributed to both meta-analyses of hazard ratios and survival probabilities when these were based on all eligible studies but only to the meta-analysis of survival probability when they were based on non-overlapping studies. n_E and n_C, number of papers retrieved from the English and Chinese databases, respectively.

Figure 2

Study-specific hazard ratios and summary pooled estimates of the effect of tumor stage on mortality after a diagnosis of esophageal cancer in China based on the subset of non-overlapping studies (Methods section): (A) stage III–IV vs stage 0–II; (B) stage III vs stage II; (C) stage II vs stage 0–I; (D) stage III vs stage 0–I; (E) stage IV vs stage 0–I; and (F) per one unit increment in stage category (stage taken as a continuous variable). Comparisons based on stage groupings with less than 5 studies are omitted. ∗The HRs reported in the original publication used late stage as the reference group; hence, HRs using early stage as the reference group were derived by inverting the reported HR values. #Several study-specific HR estimates from a single study included in the meta-analyses as they corresponded to different (nonoverlapping) patient subgroups (eg, different treatment modalities).

Figure 3

Number (%) of deaths from esophageal cancer that could potentially have been prevented in China, in 2018, among patients diagnosed in the previous 5 years, if the current stage distribution (status quo) were shifted downwards to: (i) scenario 1, the nationwide stage distribution in South Korea (30.3%, 28.6%, 26.6%, and 14.5% tumor diagnosed, respectively, at stages 0–I, II, III, and IV) and (ii) scenario 2, the stage distribution reported in the intervention arm of an intensive endoscopic screening trial in China (71.0%, 19.4%, 6.4%, and 3.2%, respectively, at stages 0–I, II, III, and IV) (estimations based on the stage distribution and stage-specific survival estimates yielded by the meta-analyses of non-overlapping studies; Text S2 provides full discussion of estimation methods and underlying assumptions).